Study: Why even targeted lung cancer therapies eventually fail

Even when patients are treated with targeted cancer therapies, many lung cancer patients suffer a recurrence. Researchers at Cold Spring Harbor Laboratory wanted to uncover how some cancers escape the power of targeted treatment. Their work was published in the journal eLife this week.
The team of scientists, lead by Raffaella Sordella, found that a tiny subset of cells in or around a cancerous tumor can change over time and become the seeds of a killer relapse.
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hamed El-Tanani
The delivery of anticancer agents to their subcellular sites of action is a significant challenge for effective cancer therapy. Peptides, which are integral to several oncogenic pathways, have significant potential to be utilised as cancer therapeutics due to their selectivity, high potency and lack of normal cell toxicity. Novel Ras protein-Regulator of chromosome condensation 1 (Ran-RCC1) inhibitory peptides designed to interact with Ran, a novel therapeutic target in breast cancer, were delivered by entrapment into polyethylene glycol-poly (lactic-co-glycolic acid) PEG-PLGA polymeric nanoparticles (N...

Abstract
OBJECTIVE: Wearable devices such as a wrist actigraph may have a potential to objectively estimate patients' functioning and may supplement performance status (PS). This proof-of-concept study aimed to evaluate whether actigraphy data are significantly associated with patients' functioning and are predictive of their survival in patients with metastatic non-small cell lung cancer.
METHOD: We collected actigraphy data for a three-day period in ambulatory patients with stage IV non-small cell lung cancer. We computed correlations between actigraphy data (specifically, proportion of time spent immobile ...

hler
Non-small cell lung cancer (NSCLC) in non-, and especially in never-smoking patients is considered a biologically unique type of lung cancer, since risk factors and tumorigenic conditions, other than tobacco smoke, come into play. In this review article, we comprehensively searched and summarized the current literature with the aim to outline what exactly triggers lung cancer in non-smokers. Changes in the tumor microenvironment, distinct driver genes and genetic pathway alterations that are specific for non-smoking patients, as well as lifestyle-related risk factors apart from tobacco smoke are critically discuss...

In the present study, we conducted high ‐throughput luciferase reporter screening to discover new Keap1/Nrf2 pathway inhibitors. From our screening, the novel compound K‐563 was isolated from the culture broth ofStreptomyces sp. 3728 ‐17 and was found to selectively inhibit the reporter activity of the Keap1/Nrf2 pathway. Furthermore, K‐563 inhibited the expression of Keap1/Nrf2 pathway downstream proteins, GSH synthesis and ROS resistance through the suppression of the Keap1/Nrf2 pathway downstream gene expression. AbstractKeap1/Nrf2 pathway regulates the antioxidant stress response, detoxification response, and e...

Abstract
The evolution of therapeutic resistance is a major cause of death for cancer patients. The development of therapy resistance is shaped by the ecological dynamics within the tumor microenvironment and the selective pressure of the host immune system. These selective forces often lead to evolutionary convergence on pathways or hallmarks that drive progression. Thus, a deeper understanding of the evolutionary convergences that occur could reveal vulnerabilities to treat therapy-resistant cancer. To this end, we combined phylogenetic clustering, systems biology analyses, and molecular experimentation to ident...

Abstract
Telomerase is an important biomarker for cancer diagnosis and a valuable target for cancer therapy. Most of the reported telomerase assays suffer from the repeating thermal cycles, laborious protocols, expensive instruments and the limited sensitivity. To solve these issues, we develop a new telomerase assay based on telomerization-driven release of fluorescent 2-aminopurine. We designed a 2-aminopurine molecular beacon in which the fluorescence of 2-aminopurine is quenched due to stacking interaction effect without the use of extra quenchers. The presence of target telomerase can open the 2-aminopurine m...

In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry andWestern blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medi...

A team of researchers at the Gene Editing Institute in Newark, Delaware, has successfully treated chemotherapy-resistant lung cancer cells with the CRISPR gene-editing technique.
The study was published Dec. 21, 2018, in Molecular Therapy Oncolytics.
In addition to making drug-resistant lung cancer cells treatable with chemotherapy, the approach offers the potential to improve quality of life for cancer patients.
“In the broader sense, such an approach would ultimately lead to a reduced level of chemotherapy required to produce the same tumor-killing activity, leading to an improvement in the quality of life of a can...

In this study, we show that calorie restriction is protective against age-related increases in senescence and microglia activation and pro-inflammatory cytokine expression in an animal model of aging. Further, these protective effects mitigated age-related decline in neuroblast and neuronal production, and enhanced olfactory memory performance, a behavioral index of neurogenesis in the SVZ. Our results support the concept that calorie restriction might be an effective anti-aging intervention in the context of healthy brain aging.
Greater Modest Activity in Late Life Correlates with Lower Incidence of Dementia
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